Ischemic stroke events are clinical manifestations of rapid loss in brain functions as a result of a lack of blood supply to the brain region due to blockages in the vascular system exemplified by thrombosis and arterial embolisms. A transient episode of ischemia causing neurological dysfunctions for a short period of time, usually less than 24 hours, is called transient ischemic attack (TIA). Rapid diagnosis and treatment of ischemic strokes can ameliorate long-term debilitating neurological damage responsible for partial or full paralysis of limbs and musculature, and/or cognitive impairments.
Common diagnostic procedures for clinical diagnosis of ischemic stroke include the use of un-infused computerized axial tomographic (CT) imaging and CT angiogram imaging to exclude intra-cerebral hemorrhage and other brain pathologies such as tumors and vascular abnormalities. The limitation with imaging studies is that only a very small percentage of cases of ischemic strokes show any change within the time window of 4.5 hours from the time of onset of stroke symptoms, a critical period during which clot-dissolving medications are useful in dissolving the clot. Therefore, in the majority of cases, a diagnosis of ischemic stroke is made by a reasonable assumption based on clinical presentations. There are numerous diseases that mimic stroke events as their presenting features. They are called stroke-mimics and include diseases exemplified by Todd's paralysis, migraine with prolonged aura, focal neurological deficits associated with hypoglycemia, and hypertensive and metabolic encephalopathies. Currently there are no quick methods available for identification of stroke-mimetic diseases for the purpose of excluding such diseases, and for making a confirmed diagnosis of ischemic stroke in an emergency presentation. Therefore, it is not clear whether all the patients that are diagnosed with ischemic stroke are actually suffering from this clinical condition. Even though magnetic resonance imaging (MRI) scans are available for clinical use, they are even more time-consuming, costly and therefore not used routinely for diagnostic purposes in emergency clinical settings.
An ischemic stroke event results in the death of brain cells at the core of the ischemic area with spread of ischemic changes to the surrounding penumbral area as the duration of the lack of blood supply to the affected regions of the brain increases. The penumbral tissue is potentially amenable to salvage by restoring blood flow. A common emergency treatment strategy to restore blood flow to the brain after an ischemic stroke is to administer intravenous infusion of tissue plasminogen activator (tPA) for augmenting dissolution of the already formed blood clots, preferably within four and a half hours after the onset of symptoms. Currently, emergency treatment protocols for strokes with different volumes of ischemic penumbra deliver the same amount of clot dissolving agent tPA per kilogram of body weight. In other words, the dosages of tPA prescribed are not based on the volume of ischemic penumbra. Moreover, tPA has very serious hemorrhagic side effects and therefore, its indiscriminate use in stroke-mimic cases is not desirable.
Clinical researchers have assessed a wide range of biomolecules released from damaged brain tissue for their potential utility as molecular markers for rapid diagnostic test for stroke events. For example, it is known by those skilled in these arts that biomolecules assessed for their potential usefulness as stroke biomarkers include glial fibrillary acidic protein, protein S-100B, myelin basic protein, C-reactive protein, neuron-specific enolase, S100β, soluble thrombomodulin, capsase 3, tau protein, fatty acid protein, nucleic acids, autoantibodies to N-methyl D-aspartic acid, metalloproteinase-9, L-arginine, plasma glutamate levels, pro-inflammatory cytokines, neuro-inflammatory markers, and interleukin-6 among others. Additionally, the usefulness of detecting and measuring Parkinson 7 protein and nucleoside diphosphate kinase A in cerebrospinal fluid was examined. However, a comparative study by Jauch et al. (2006, Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke 37:2508-2513) concluded that none of the biomarkers referred to above were found to be sufficiently reliable for use in clinical medicine, and the authors were unable to identify a clinically useful biomarker for rapid detection of the occurrence of a stroke event.